The objectives of this program are to investigate the biosynthesis of glycosaminoglycans and proteoglycans with the eventual aim of facilitating a better understanding of the pathogenesis of connective tissue diseases and a better understanding of the processes of development and aging of connective tissues. Microsomal preparations from chick embryo cartilage are being utilized with sugar nucleotide precursors and PAPS to delineate the pathway of chondroitin sulfate biosynthesis. Microsomal preparations from mouse mast cell tumors are being utilized with appropriate radioactively-labeled sugar nucleotide precursors and PAPS to delineate the pathway of heparin biosynthesis. Tissue cultures of mast cells, which produce both heparin and chondroitin sulfate are being utilized to investigate the subcellular sites of glycosamino-glycan and proteoglycan biosynthesis. Radioactive precursors will be utilized to pre-label the cells before obtaining subcellular fractions. Work will include further description of the mechanism of glycosaminoglycan assembly and sulfation. Synthesis of microsomal proteoglycan will be examined.